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Molecular Genetics Laboratory

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Pitt Hopkins - TCF4 Deletion and Duplication Analysis

  • LIS Mnemonic: MBTCF4DEL


    Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA is also acceptable.

    Volume Required

    5 ml whole blood or 1 ug extracted DNA

    Minimum Required

    3 ml whole blood


    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.


    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm


4-6 weeks



Disease Information

Clinical Features:

Pitt Hopkins Syndrome (PTHS) is characterized by severe mental retardation, deep set eyes, broad and beaked nasal bridge, wide mouth, cupid’s bow upper lip, a protruding lower face and intermittent hyperventilation followed by apnea. In addition, patients can show a happy personality, stereotypic movements which in addition to microcephaly, breathing anomalies, mental retardation and seizures resemble the features seen in both Rett and Angelman syndromes. Hirschsprung disease and constipation overlap with features observed in Mowat-Wilson syndrome.

Molecular Genetics:

TCF4 is located on chromosome 18q21.2 and it encodes a member of the bHLH transcription factor family. Missense, splice site, nonsense and large deletions have been identified in the TCF4 gene (Zweier et al. 2007, Zweier et al. 2008).

Test Methods:

Large deletions and duplications will be detected using multiplex ligation-dependent probe amplification assay (MLPA).

Detection Rate:

Point mutations in TCF4 were identified in 14-35% of patients with severe mental retardation and clinical findings overlapping with PTHS (Zweier et al. 2008; De Pontual et al. 2009) while deletions have been detected in 13% of patients initially evaluated for Angelman, Mowat-Wilson, or Rett syndrome whose phenotype overlapped PHS (Giurgea et al. 2008). REFERENCES de Pontual., Hum Mutat. 2009 Apr;30(4):669-76 Giurgea et al. Hum Mutat. 2008 Nov;29(11):E242-51. Zweier et al., Am J Hum Genet. 2007 May; 80(5): 994–1001 Zweier et al ., J Med Genet. 2008 Nov;45(11):738-44

Related Tests:

Sequence and deletion/duplication analysis of MECP2, CDKL5, FOXG1, and UBE3A. Sequence analysis of SLC9A6. Methylation-sensitive PCR for Angelman Syndrome.


Test results with interpretation will be mailed and/or faxed to the referring physician or laboratory following completion of the test. Additional reports will be provided as requested.


The clinical utility of such testing is to support a clinical diagnosis of the disease, facilitate genetic counseling, assess the risk to other first degree relatives and to facilitate testing of at - risk family members.

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